Cardurion Pharmaceuticals reveals breakthrough results in heart failure treatment with PDE9 inhibitor

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In a significant development for cardiovascular disease treatment, Cardurion Pharmaceuticals, Inc., a clinical-stage biotechnology company, has presented positive results from its Phase 2 proof-of-concept clinical trial, CARDINAL-HF. This trial tested CRD-740, a phosphodiesterase-9 (PDE9) inhibitor, showcasing its potential to become a new standard of care in heart failure therapy. These findings were revealed at the Annual Congress of the Heart Failure Association of the European Society of Cardiology held in Lisbon, Portugal from May 11-14.

The CARDINAL-HF Phase 2a trial met its primary endpoint, demonstrating a statistically significant median increase in plasma cyclic guanosine monophosphate (cGMP) after four weeks of treatment among patients with heart failure with reduced ejection fraction (HFrEF). cGMP serves as a biomarker for the activity of the protective myocardial natriuretic peptide (NP) signaling pathway, crucial for its clinically proven benefits in heart failure management.

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Key Trial Outcomes:

– CRD-740 showed a significant increase in both plasma and urinary cGMP levels, compared to a placebo, affirming its efficacy in inhibiting PDE9 and enhancing NP signaling pathway activity.

– The trial established CRD-740’s safety profile, with the treatment being well-tolerated among participants, suggesting its suitability for further clinical testing.

James Udelson, MD, Chief of Cardiology at Tufts Medical Center and Principal Investigator for the CARDINAL-HF trial, expressed optimism about the trial’s success, stating, “These very promising data represent an important next step in the development of this novel mechanism. The results are impressive, showing robust PDE9 inhibition with significant increases in plasma and urinary cGMP, along with a favorable safety profile.”

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Expanding Treatment Possibilities:

Based on these encouraging results, Cardurion has initiated two additional Phase 2 clinical trials involving 640 patients. These include a dose-ranging trial in patients with HFrEF and a proof-of-concept trial in patients with heart failure with preserved ejection fraction (HFpEF). This expansion underscores the potential of CRD-740 to serve as both a monotherapy and a complementary treatment alongside existing heart failure medications like sacubitril/valsartan.

Peter Lawrence, CEO of Cardurion Pharmaceuticals, highlighted the broader implications of the PDE9 inhibition mechanism, stating, “The data suggest that PDE9 inhibition has the potential to provide benefit to patients when administered alone or in combination with guideline-directed medical therapy, and ultimately become standard of care for patients with both types of heart failure.”

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As Cardurion Pharmaceuticals continues to explore the therapeutic potential of PDE9 inhibitors, the heart failure treatment landscape may be poised for a significant shift, offering new hope and improved outcomes for millions battling this chronic and debilitating condition.

The potential integration of PDE9 inhibitors into the heart failure treatment paradigm could represent a transformative advancement, particularly given the ongoing challenges and high morbidity associated with the disease. Continued research and subsequent trials will be crucial to fully understand and harness the benefits of this promising therapeutic approach.


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